Fungal mediated generation of mammalian metabolites of fenofibrate and enhanced pharmacological activity of the main metabolite fenofibric acid.

Different fungi viz. Aspergillus niger NCIM 589, A.ochraceous NCIM 1140, Cunninghamella blakesleeana NCIM 687, C. echinulata NCIM 691, Rhizopus stolonifer NCIM 880, Mucor rouxi MTCC 386, Trichothecium roseum NCIM 1147 were screened for their potential to biotransform anti-hyperlipidemia and anti-hypertriglyceridemia drug, fenofibrate to fenofibric acid, the active metabolite and other mammalian metabolites. Among the fungi screened C. blakesleeana transformed fenofibrate to fenofibric acid and other three metabolites. HPLC, LC-MS/MS analysis and previous reports confirmed the transformation of fenofibrate and metabolites as fenofibric acid (M1), reduced fenofibric acid (M2), reduced fenofibric acid taurine conjugate (M3), reduced fenofibric acid ester glucuronide (M4), the mammalian metabolites reported previously. The results proved the potential of C.blakesleeana NCIM 687 in the production of mammalian phase I (M1 and M2) and phase II (M3 and M4) metabolites in large quantities and also as an in vitro model for drug metabolism studies.

Factors influencing the production of hydrogen by the purple non-sulphur phototrophic bacterium Rhodopseudomonas acidophila KU001.

Rhodopseudomonas acidophila KU001 was isolated from leather industry effluents and the effect of different cultural conditions on hydrogen production was studied. Anaerobic light induced more hydrogen production than anaerobic dark conditions. Growing cells produced more amounts of hydrogen between 96 and 144 h of incubation. Resting and growing cells preferred a pH of 6.0 ± 0.24 for hydrogen production. Succinate was the most preferred carbon source for the production of hydrogen while citrate was a poor source of carbon. Acetate and malate were also good carbon sources for hydrogen production under anaerobic light. Among the nitrogen sources, R. acidophila preferred ammonium chloride followed by urea for production of hydrogen. L-tyrosine was the least preferred nitrogen source by both growing and resting cells.

Potential of thermophilic fungus Rhizomucor pusillus NRRL 28626 in biotransformation of antihelmintic drug albendazole.

In the present investigation, thermophilic fungus Rhizomucor pusillus was used to study biotransformation of antihelmintic drug albendazole to produce its active metabolite, albendazole sulfoxide and novel metabolites of commercial interest. A two-stage fermentation procedure was followed for biotransformation of albendazole. The transformation was identified and structures were confirmed by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analysis. Four metabolites albendazole sulfoxide, the active metabolite, albendazole sulfone, N-methyl metabolite of albendazole sulfoxide, and a novel metabolite were produced. The study demonstrates the biotransformation ability of thermophilic fungus R. pusillus NRRL28626 in the production of, the active metabolite of albendazole which has industrial and economic importance, other metabolites and a novel metabolite in an ecofriendly way.

Microbial transformation of albendazole.

Screening scale studies were performed to biotransform anthelmintic drug albendazole by using twelve bacterial strains representing six genera and five actinomycetes cultures. Among the cultures studied, Bacillus subtilis MTCC 619, Escherichia coli MTCC 118 and Klebsiella pneumoniae MTCC 109 could transform albendazole to one metabolite whereas, Enterobacter aerogenes NCIM 2695, Klebsiella aerogenes NCIM 2258, Pseudomonas aeruginosa NCIM 2074 and Streptomyces griseus NCIM 2622 could transform albendazole into two metabolites in significant quantities. The transformation of albendazole was identified by HPLC. Based on LC-MS-MS data, the two metabolites were predicted to be albendazole sulfoxide (M1) and albendazole sulfone (M2), the major mammalian metabolites reported previously. Since M1 is active metabolite, the results prove the versatility of microorganisms to perform industrially attractive chemical reactions.

Studies on microbial transformation of meloxicam by fungi.

Screening-scale studies were performed with 26 fungal cultures for their ability to transform the anti-inflammatory drug meloxicam. Among the different fungi screened, a filamentous fungus, Cunninghamella blakesleeana NCIM 687, transformed meloxicam to three metabolites in significant quantities. The transformation of meloxicam was confirmed by high-performance liquid chromatography (HPLC). Based on the liquid chromatography-tandem mass spectrometry (LC-MS/MS) data, two metabolites were predicted to be 5-hydroxymethyl meloxicam and 5-carboxy meloxicam, the major mammalian metabolites reported previously. A new metabolite was produced, which is not detected in mammalian systems. Glucose medium, pH of 6.0, temperature of 27 degrees , 5-day incubation period, dimethylformamide as solvent, and glucose concentration of 2.0%were found to be suitable for maximum transformation of meloxicam when studied separately. It is concluded that C. blakesleeana can be employed for biotransformation of drugs for production of novel metabolites.

Production of lipases by four anoxygenic purple non-sulphur phototrophic bacteria.

Production of lipases by Rhodopseudomonas palustris, Rhodobacter sphaeroides, Rhodocyclus gelatinosus and Rhodocyclus tenuis in different synthetic media was investigated. Rc. gelatinosus followed by Rb. sphaeroides were good producers of lipases, while Rps. palustris and Rc. tenuis were poor in lipase secretion. Lipase secretion by Rc. gelatinosus was adaptive in nature, while other three bacterial behavior was inconsistent. No positive correlation could be observed between growth and lipase production.